Disease Control, Adverse Events Drive Upadacitinib Dose Adjustments For Atopic Dermatitis

A new study shows that upadacitinib dose changes for atopic dermatitis are more common among patients starting at 30 mg—largely due to adverse events and treatment responses—whereas dose escalations from 15 mg are mainly due to insufficient disease control.1

These data and others were highlighted in a recent analysis authored by Flavia Manzo Margiotta, MD, from the University of Pisa Department of Dermatology, alongside a team of other investigators. The team noted that dose adjustments based on patients’ responses and tolerance can enhance their adaptability to clinical variations with time.2

However, Margiotta and colleagues highlighted that despite the increasing utilization of upadacitinib for atopic dermatitis, real-world information related to dose adjustments’ rationale, timing, and outcomes had been limited prior to this study.

“In this context, a structured and evidence-based approach to dosing transitions – either escalation or de-escalation – could significantly improve personalized treatment planning and long-term disease management,” Margiotta et al wrote.1 “To address this gap, our study aimed to evaluate upadacitinib dose adjustments in adult [atopic dermatitis] patients.”

Trial Design Details

The investigative team determined that a systematic, data-driven strategy for adjusting doses—either escalation or reduction—could help give patients with this inflammatory skin condition more tailored treatment approaches. To this end, the study investigators looked into dose modifications of upadacitinib in adults with atopic dermatitis at 6 dermatology centers.

Their analysis was done at centers located in Tuscany, Italy, with patients treated with upadacitinib between May 2022 - March 2025 being included as trial subjects. The investigative team's focus was on relationships between dose level, clinical features, and drug survival. Their protocol for the analysis was approved by the Comitato Etico Regionale per la Sperimentazione Clinica della Toscana – AREA VASTA SUD EST on in May 2022.

Margiotta and coauthors' statistical testing for the participants' data involved chi-squared tests, Mann–Whitney or Student’s t-tests, and Kaplan–Meier survival analyses, all of which they performed through R software version 4.3.2. They recruited 58 patients in total, with 53.4% being listed as male and 46.6% as female. The subjects all had a mean age of 32.3 ± 12.7 years. The ages of subjects were capped at 65 years.

Findings on Upadacitinib Dose Adjustments

Among these participants, it was noted by Margiotta et al that 69.0% initiated treatment with upadacitinib at a 15 mg dose. They also highlighted that 31.0% began on a 30 mg dose. In the team's baseline analysis, their findings demonstrated that those beginning on the 30 mg dose of upadacitinib had significantly higher Eczema Area and Severity Index (EASI) scores as opposed to patients in the 15 mg arm of the study (23.33 versus 18.08, P = .038).1 This, they noted, suggested greater disease severity.

No significant differences at baseline were identified by Margiotta and colleagues in patients' family histories, demographics, age of disease onset, or distribution of atopic dermatitis phenotypes, except that neck involvement was more common in the 15 mg arm (P = .044). Across their observation period, the investigators noted that 24 dose changes took place. Adjustments were proportionally more common in the 30 mg cohort, where 44.8% needed a modification compared to 20.8% in the 15 mg cohort.

The predominant reasons for reducing from 30 mg were adverse events (AEs). AEs were reported in 31% of the study subjects, and attainment of minimal disease activity (MDA) was noted in 17.2%. The 9 AEs were documented after a mean of 13.1 ± 8.5 weeks, with Margiotta et al demonstrating that these events consisted of acneiform eruptions in 44.4% of participants, hypercholesterolemia or hyperlipidemia among 33.3%, neutropenia or leukopenia among 22.2%, and asthenia in 11.1%.

Among those who had diminished their dose as a result of AEs, it was found that 77.8% had already attained MDA. Additionally, the investigative team concluded that more than half (57.1%) maintained MDA thereafter. In contrast, the only driver of dose escalation from 15 mg was shown by the team to be inadequate disease control, with 21.2% needing an increase to 30 mg after an average of 34.8 ± 26.5 weeks, and 40% of these attaining MDA following escalation.

“Future studies should investigate predictive markers for AEs and response, as done for biologics,” the investigators wrote.1 “In conclusion, these real-world results highlight the effectiveness, safety, and flexibility of upadacitinib, supporting its role in the personalized management of moderate-to-severe [atopic dermatitis].”

References

1. Manzo Margiotta F, Dini V, Cartocci A, et al. Upadacitinib dose adjustment in moderate-to-severe atopic dermatitis: insights from a multicenter real-world study. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. https://doi.org/10.1111/ddg.15908.

2. Ebata T. Dose flexibility of oral Janus kinase inhibitors for long-term control of atopic dermatitis. Br J Dermatol. 2023; 188: 165.